Model-based precision dosing of sirolimus in pediatric patients with vascular anomalies

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Tomoyuki MizunoAlexander Vinks

Abstract

Sirolimus is the first drug to show efficacy in the treatment of patients with complicated vascular anomalies. The current study expands on the evolution of a PK model-based strategy for the precision dosing of sirolimus as part of prospective concentration controlled clinical trials in pediatric patients with vascular anomalies. Twelve month follow up data collected from 52 pediatric patients participating in the Phase 2 clinical trial were analyzed. Target attainment across the age range of 3weeks to 18years after 2-3months of therapy was 94% (49 out of 52 patients). The mean sirolimus dose to achieve the target of ~10ng/mL for patients older than 2years was 1.8mg/m2 twice daily (range 0.8-2.9), while it was 0.7 to 1.6mg/m2 twice daily for patients 3weeks of age to 2years. A total of 676 blood concentration data were used for the population PK analysis by nonlinear mixed effect modeling using NONMEM. The final model included a maturation function for sirolimus clearance and allometrically scaled body weight to account for size differences. The mean allometrically scaled sirolimus clearance estimates increased from 3.9 to 17.0L/h per 70kg with age from shortly after the birth to 2years of age while the mean estimate for patien...Continue Reading

Citations

Sep 12, 2018·Journal of Clinical Pharmacology·Joshua C EuteneuerHenry T Akinbi
Sep 25, 2018·Journal of Clinical Pharmacology·Michael NeelyAndrea Edginton
Jan 21, 2020·Pediatric Dermatology·Melissa DoddsSheilagh Maguiness
Feb 19, 2020·Pathology International·Yumiko HoriEiichi Morii
Jun 16, 2018·Human Molecular Genetics·Dong LiHakon Hakonarson
Jun 13, 2020·British Journal of Clinical Pharmacology·Tomoyuki MizunoAlexander A Vinks
May 20, 2020·Therapeutic Drug Monitoring·Joshua C EuteneuerAlexander A Vinks
Jun 27, 2019·Advances in Wound Care·Michio Ozeki, Toshiyuki Fukao
Jun 20, 2020·American Journal of Clinical Dermatology·An Van DammeMiikka Vikkula
Jan 29, 2020·Ophthalmic Plastic and Reconstructive Surgery·Marissa K ShojiSuzanne K Freitag
Aug 12, 2020·Cardiology in the Young·Sylvia KrupickovaRaad Mohiaddin
Dec 15, 2020·Pediatric Neurology·Alison J SeboldAnne M Comi
Feb 1, 2020·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Xiaojun CaiZheng Jiao
Mar 13, 2021·Frontiers in Pediatrics·Alan AbdullaMatthijs de Hoog
Nov 25, 2020·The Journal of Pediatrics·Shogo John MiyagiSonya Tang Girdwood
Jun 25, 2021·Circulation Research·Angela QueisserMiikka Vikkula
Jun 30, 2021·Journal of Clinical Pharmacology·Alexander A Vinks, Jeffrey S Barrett
Mar 30, 2019·Journal of Vascular Surgery·Arash FereydooniNaiem Nassiri

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.